Abstract
The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes.
Highlights
Thousands of different life-related biochemical processes, such as cell respiration and many other metabolic reactions, can lead to the production and utilization of energy in forms of ATP synthesis and heat release [1,2,3]
The central set of reactions involved in cellular fuel homeostasis are collectively known as the citric acid or tricarboxilic acid cycle (TCA cycle), which oxidizes the products of glycolisis and lipid-derived substrates, such as acetyl-CoA, to produce energy in the mitochondria [1]
The glyoxylate cycle allows these organisms to use fats for the synthesis of carbohydrates via the acetate generated during fatty acid β-oxidation, which is achieved by two unique enzymes: isocitrate lyase (ICL; EC 4.1.3.1) and malate synthase (MS; EC 2.3.3.9)
Summary
Thousands of different life-related biochemical processes, such as cell respiration and many other metabolic reactions, can lead to the production and utilization of energy in forms of ATP synthesis and heat release [1,2,3]. The glyoxylate cycle allows these organisms to use fats for the synthesis of carbohydrates via the acetate generated during fatty acid β-oxidation, which is achieved by two unique enzymes: isocitrate lyase (ICL; EC 4.1.3.1) and malate synthase (MS; EC 2.3.3.9). These enzymes sequentially catalyse chemical conversions, which are involved in the glyoxylate cycle and appear to be absent or unfunctional in most circumstances in vertebrates, including rodents [7,8,9], guinea pigs [10] and humans [11]
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